The inflammatory skin disease map (ISD map): an interactive computational resource focused on psoriasis and atopic dermatitis molecular mechanisms
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Abstract
Background
Inflammatory skin diseases (ISD), including atopic dermatitis (AD) and psoriasis (PsO), emerge from a complex network of inter- and intracellular biochemical interactions under the influence of genetic and environmental factors. The complexity of ISD mechanisms hinders translation of research findings into effective treatments and may explain the low remission rates despite the availability of modern targeted therapies.
Objective
To model AD- and PsO-associated mechanisms as networks of context-specific molecular interactions, the so-called ISD map, and to check the usefulness of this map as a graphically guided review of AD and PsO mechanisms and as a mechanistic hypothesis-generating platform.
Methods
The ISD map was built by assembling mechanistically resolved causal interactions obtained from relevant biomedical literature via manual curation.
Results
We demonstrate that the ISD map ( https://imi-biomap.elixir-luxembourg.org/ ) serves as an interactive, graphical review of AD and PsO molecular mechanisms and as a mechanistic hypothesis-generating platform. By analysing the map structure itself or the map integrated with genetics and functional genomics data, we could generate the following mechanistic hypotheses: (i) AD poor response to dupilumab is associated with a potential upregulation of IFNG, IL22, TSLP, IL-17A and IL25 signalling pathways in keratinocytes and/or single nucleotide polymorphisms (SNPs) in genes encoding regulators of IFNG expression in Th1 cells and (ii) PsO resistance to cytokine-induced apoptosis is associated with SNPs in IFNG signalling genes regulating SOCS1 in keratinocytes. Finally, the IL4/IL13 pathway in the AD submap of the ISD map was converted into a probabilistic Boolean model to simulate the effects of IFNG in sensory perception of itching after treatment with dupilumab. Our findings suggest that inhibiting both IFNG and IL4R may improve the therapeutic management of itching.
Conclusion
The ISD map provides a significant interactive, computationally accessible resource of molecular knowledge on AD and PsO that can be used to graphically review known AD and PsO mechanisms and generate mechanistic hypotheses.
Article activity feed
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In AD, initial trigger factors elicit keratinocytes (KCs) to release proinflammatory molecules that184activate immune cells such as ILC2 cells (see “ILC2 cells activation by keratinocytes” in the map
As you note, there are potential drivers of AD and psoriasis. I know this may be asking a lot, but it would be useful to see how these pathways amplify immune signaling by allowing the user to “initiate” an upstream event and, in a temporal fashion, watch as it propagates through the nodes of the system leading to consequences that reinforce the disease state.
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The ISD map was built based on the review of 460 AD- and 110 PsO-related articles
This is great resource to help display and condense the complexity of the etiology and maintenance of AD and psoriatic disease states. I may be missing this in your interactive tool, but it would be helpful to include the publications used to develop each node of the model as a link when selecting any particular node. Given the sometimes conflicting information available for association vs. causal factors in the literature, the links would be helpful to place particular weights on any given node.
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I don't understand what you mean by "found in the AD map"?
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Hi! I'm not sure what this means. Could you give a one-sentence explainer of "systems biology standards" for the non-systems biologists?
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